宿主lncRNA4调控流感病毒复制的作用机制

Influenza A virus(IAV) infection poses a significant threat to human health. The research about the interaction between virus and host will promote the development of IAV prevention and control. Long noncoding RNAs (lncRNAs), a hot research field at present, play important roles in epigenetic, transcriptional and post-transcriptional levels, but were known little in the IAV replication. Our preliminary study had found that lncRNA4 was involved in the transcription and replication of IAV RNA to regulate viral infectivity. In this proposed work, we will study the biological function about lncRNA4 on IAV replication, illustrate how it affects IAV replication, determine lncRNA4 important molecular structure, and further explore its mechanism from two aspects of virus and host factors. The objective of this work are not only to provide theoretical basis for development of novel antiviral drugs, but also to promote further study on molecular mechanism of lncRNAs in the regulation of viral replication.

甲型流感病毒（IAV）感染严重威胁着人类健康，加强病毒宿主相互作用的基础研究将推动IAV防控策略的发展。长链非编码RNA（lncRNAs）在表观遗传、转录及转录后水平上执行着重要生物学功能，已成为各领域的研究热点，但目前对lncRNAs在IAV复制中生物学功能的了解依然非常有限。我们的前期工作发现lncRNA4参与IAV基因组RNA的转录与复制，调控病毒的感染性。本课题拟依据前期工作基础，研究lncRNA4在IAV复制过程中的生物学功能及其特异性，明确其参与病毒基因组RNA转录复制的作用环节及分子结构基础，并分别从病毒和宿主两方面因素深入探索其作用机制。本研究将为lncRNAs调控病毒复制机制这一全新领域的深入研究奠定基础，同时为发现新的抗病毒药物靶标提供重要的理论依据。

甲型流感病毒（IAV）感染严重威胁着人类健康。IAV的高效复制严格依赖于宿主因子，然而关于宿主长链非编码RNA(lncRNAs)参与IAV感染的研究还非常有限。本工作中，我们开展了lncRNAs在IAV复制中的生物学功能和分子机制的研究，研究结果包括：.1）.应用靶向人源lncRNAs的esiRNA库进行高通量筛选，获得了一系列参与调控IAV复制的功能性lncRNAs，并对其中的lncRNA IPAN和PAAN做进一步的功能验证和机制研究。.2）.证明了IPAN能被IAV诱导表达并劫持，通过与病毒RNA依赖的RNA聚合酶（RdRp）组分PB1蛋白结合来抑制RIG-I介导的PB1降解。.3）.证明了PAAN通过促进病毒RNA聚合酶复合物的形成，增强RdRp的活性，从而保证了病毒RNA的高效合成。.这一工作揭示了宿主lncRNAs在病毒感染中的新功能，它们可以被病毒劫持，来对抗宿主的免疫应答或者促进病毒自身的复制。该研究为新抗病毒疗法的发展提供了新的思路。